Chloroform (CHC13) was significantly more potent in producing kidney necrosis and depleting kidney glutathione (GSH) than was deuterium labeled chloroform (CDC13). CHC13 also produced a greater decrease in the level of kidney GSH in DBA mice, which are more sensitive to the kidney toxic effect of CHC13 than it did in the insensitive C57 mice. These results indicate one of the rate determining steps in the kidney necrosis produced by CHC13 is the metabolism of its C-H bond. This finding is consistent with CHC13 being bio-transformed into the toxic metabolite phosgene (COC12) in the kidney. This metabolite can possibly react with vital tissue components to produce necrosis or be detoxified by reacting with GSH to yield digluthionyl-dithiocarbonate (GSCOSG)